Genetic Variant ENST00000367903.7:c.69+5382G>T (chr1-163212144-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000367903.7(RGS5):c.69+5382G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,132 control chromosomes in the GnomAD database, including 1,499 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1499 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

RGS5
ENST00000367903.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

Publications

5 publications found

Variant links:

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5 links:

RGS5-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

RGS5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367903.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
RGS5	NM_001414472.1	c.65+36386G>T	intron	N/A	NP_001401401.1
RGS5	NM_001414473.1	c.65+36386G>T	intron	N/A	NP_001401402.1
RGS5	NM_001414474.1	c.65+36386G>T	intron	N/A	NP_001401403.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS5	ENST00000367903.7	TSL:3	c.69+5382G>T	intron	N/A	ENSP00000356879.3	B1APM2
RGS5	ENST00000618415.4	TSL:4	c.-280-43776G>T	intron	N/A	ENSP00000480891.1	O15539-2
RGS5-AS1	ENST00000415437.1	TSL:2	n.1754C>A	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20869

AN:

152008

Hom.:

1500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.0390

Gnomad SAS

AF:

0.0734

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.133

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.137

AC:

20880

AN:

152126

Hom.:

1499

Cov.:

AF XY:

0.137

AC XY:

10156

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.133

AC:

5540

AN:

41508

American (AMR)

AF:

0.140

AC:

2135

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

462

AN:

3466

East Asian (EAS)

AF:

0.0387

AC:

201

AN:

5188

South Asian (SAS)

AF:

0.0738

AC:

356

AN:

4822

European-Finnish (FIN)

AF:

0.156

AC:

1649

AN:

10576

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10133

AN:

67970

Other (OTH)

AF:

0.132

AC:

278

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

914

1829

2743

3658

4572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.139

Hom.:

2535

Bravo

AF:

0.136

Asia WGS

AF:

0.0790

AC:

273

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.6

(source)

DANN

Benign

0.82

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over